Respiratory diseases are some of the most common disorders in the world. Such respiratory diseases included conditions such as COPD, asthma, cystic fibrosis and pulmonary fibrosis. Chronic obstructive pulmonary disease (COPD), for example, affects millions of people and is responsible for extensive morbidity and mortality in the United States. COPD is a term used to describe chronic lung diseases characterized by progressive development of airflow limitation that is usually not fully reversible with medication. The common symptoms of COPD include breathlessness, wheezing and a chronic cough.
Asthma is another example of a chronic lung disease with symptoms similar to COPD, such as breathlessness and wheezing, but etiologically distinct from COPD. Asthma is a prevalent health care problem; it affects millions in the United States and around the world. About 40% of patients with asthma can be classified as having moderate to severe asthma and would benefit from more frequent monitoring of their airway inflammation. Although COPD and asthma require different treatments, test results for COPD and asthma often overlap.
Asthma in particular is characterized by an inflammatory reaction in hyper-reactive airways that restrict airflow into the lungs. In recent years, measurement of exhaled nitric oxide (eNO) has been shown to be a non-invasive and complementary tool to other pulmonary function tests in assessing airway inflammation, specifically in subjects with asthma. Accordingly, the presence of eNO has become a well-known, globally accepted biomarker for airway inflammation.
Nitric oxide is produced endogenously in cells by NO synthase and secreted by eosinophils in the distal alveoli. Its production is increased in response to inflammatory cytokines (which is associated with asthmatic episodes), and exhaled NO is thought to be an indirect measurement of airway eosinophilic inflammation. Thus, nitric oxide exhaled from the lower airways (e.g. non-nasal airways) can be correlated with the degree of airway inflammation. Patients with asthma have high levels of NO in their exhaled breath. Nitric oxide levels increase prior to the presence of clinical symptoms and its levels decline in response to appropriate therapy as airway inflammation subsides. These two characteristics make this an ideal biomarker for managing asthma status. For this reason, in 2011, the American Thoracic Society (ATS) issued new guidelines recommending the measurement of exhaled nitric oxide for the diagnosis and management of asthma. A diagnosis of asthma can be made when the level of nitric oxide in exhaled breath exceeds 50 ppb. High eNO levels are also associated with other inflammatory respiratory conditions.
In diagnosing respiratory diseases, a series of tests are routinely conducted. A common pulmonary function test (PFT) is spirometry, which measures obstruction of an individual's airway. A decreased maximum/forced lung exhalation rate often suggests airway obstruction. Results from the spirometry test can be used to estimate lung function and aid in assessing respiratory diseases and conditions. In the spirometry test, the patient expels air forcefully into a device to measure the amount (volume) of air or the air speed (flow) exhaled in one complete breath. The commonly used techniques to measure eNO require a subject to exhale into a device containing an NO sensor (online) or into a reservoir that can be analyzed later (offline). Since the concentration of eNO is inversely related to flow rate where lower exhalation rates allow more time for eNO to enter from the airway, the eNO test requires a user to exhale at a steady flow rate, normally at 50 ml/sec. As describe above, the level of eNO, measured in parts per billion (ppb), is significantly higher among asthmatic patients compared to healthy individuals.
Although the spirometry test is a common method of measuring airflow obstruction and can facilitate the monitoring of pulmonary disorders, the overlapping results in some conditions of COPD and asthma limit the use of the spirometry test alone for differentiating COPD from asthma. Additional investigations employing eNO tests, CT scans or pulse oximetry are also commonly employed to aid in assessing pulmonary diseases and conditions.
There are a number of challenges in current pulmonary function testing. Pulmonary function tests employ devices that are typically large and require the patient to be present in the physician's office or in the hospital for the tests. Moreover, the tests require separate devices, since in assessing respiratory disorders and conditions, separate measurement protocols are required for spirometry and for eNO testing. Typically, NO is measured in a clinical setting at a hospital or a physician's office for diagnostic purposes. The devices are expensive to purchase and maintain. Patients who have the most to gain from regular NO monitoring do not have regular access to accurate NO measuring equipment without frequent visits to their doctors. Thus, for at least the millions of people with moderate to severe asthma, there is a need for a cost-effective device that allows weekly or daily NO monitoring at home
Another challenge in current standard pulmonary function testing is the accuracy and efficiency of the testing. An effective eNO test would be complimentary to the standard tests, but there is a dearth of inexpensive sensors capable of detecting the minute amounts of NO (typically measured in parts per billion) present in exhaled air. Moreover, NO sensors need to provide an accurate NO measurement in the presence of other possibly interfering gas components, including water and carbon dioxide (CO2). A further challenge for NO measurement is the difficulty in distinguishing between nitric oxide (NO) and nitrogen dioxide (NO2) in a patient's breath. That is, the gas introduced from the patient's breath typically has concentrations of NO, NO2, carbon monoxide (CO), and oxygen (O2). Traditional sensors are often unselective or incapable of distinguishing between the two main NOx components of interest, NO and NO2, resulting in erroneous readings.
Thus, it would be desirable and advantageous to provide an accurate, efficient and portable respiratory monitor capable of conducting multiple pulmonary function tests, as well as other associated measurements, in a single device. It would also be desirable and advantageous to provide such a device that further allows for the remote monitoring of testing data, thereby avoiding the necessity for patients to make trips to doctor offices and hospitals. Additionally, it would be desirable and advantageous to provide such a respiratory monitor that allows for correlation of respiratory data to other relevant environmental data that can be presented in an efficient and easily understandable format.